The possibility of using ultrasound to enhance cancer gene therapy will be evaluated. Preliminary research has demonstrated that ultrasound interacting with gas bubbles in tissue can induce some cells which avoid lysis to take up large molecules, such as DNA vectors, and that these cells can survive to express gene products. Application of this phenomenon to can gene therapy should avoid use of viral vectors, allow transfection of multiple large plasmids, focus treatment on the tumor target, and combine massive tumor ablation with high efficiency transfection of survival cells. Another favorable consideration is that needed ultrasound equipment, including shockwave generation systems for lithotripsy, is already available in most large medical centers. Three specific aims are: already available in most large medical centers. Three specific aims are: (1) to experiment with the delivery of DNA plasmids and gas bubbles to tumors for optimizations of the tumor ablation and transfection-enhancement processes, (2) to demonstrate cancer gene therapy with plasmids of established therapeutic value, such as are being developed for immunotherapy, in different mouse tumor models and (3) to develop the ultrasound enhancement protocol including ultrasound guidance of injection, variation of ultrasound parameters, treatment monitoring by acoustic cavitation emissions, and imaging of tumors for complete treatment coverage. Finally, the method will be matched and oriented for application to difficult clinical situations which require new approaches to successful management. This research will provide a bridge from the basic research breakthrough to specific therapeutic applications and urgently needed clinical research programs utilizing this novel technology.